The Promise of Prevention and Early Diagnosis

Despite many decades of investigation and progress made in early diagnosis and treatment, the exact causes of
most cancers remain unknown. For most of the cancers we treat, there exists a mix of genetic changes and numerous environmental influences
that challenge the development of simple prevention strategies. NCI's approach to cancer prevention is defined by the use of advanced tools
and technologies—such as those employed in genomics, proteomics, and metabolomics—to dissect the molecular events associated
with the molecular mechanisms and early signs of cancer development.

Obesity and Cancer

The Transdisciplinary Research on Energetics and Cancer (TREC) integrates the study of diet, weight, and physical activity and their
effects on cancer by focusing on energy balance and energetics (the study of the flow and transformation of energy through living systems).
NCI currently funds four research centers and one coordinating center as part of the TREC initiative. The TREC centers are fostering
collaboration among transdisciplinary teams of scientists with the goal of accelerating progress toward reducing cancer incidence,
morbidity, and mortality associated with obesity, low levels of physical activity, and poor diet. They also provide training opportunities
for new and established scientists who can carry out integrative research on energetics and energy balance. The TREC initiative complements
NCI's other energy balance research endeavors and efforts
of the NIH Obesity Task Force.

A new era of cancer prevention will require understanding genetic alterations, both those we are born with and those we accumulate
throughout our lifetime, which can alter protein expression patterns and cellular function. These events will be further impacted by the
need to understand environmental exposures and lifestyle factors. All of these layers point to the difficulty of finding effective, nontoxic
preventive agents. Part of the solution involves identifying biomarkers of risk, as well as genome-wide association studies. For example,
NCI's Early Detection Research Network is supporting researchers who are making
important inroads in this area, including, promising preliminary work on an
early detection assay for pancreatic
cancer. Despite the complexity, NCI's extensive cancer prevention research program has generated some remarkable success stories,
including the dramatic drop in smoking rates over the past two decades, as well as the approval of tamoxifen and raloxifene for the
prevention of breast cancer. Thus, we continue to support research into lifestyle and environmental factors that influence cancer risk.
These efforts include anti-obesity programs aimed at minorities conducted under the auspices of the
Transdisciplinary Research on Energetics in Cancer (TREC) program as
well as the development of new chemopreventive agents.

Prevention is, and will continue to be, an integral part of reducing cancer's burden. Identifying and quantifying an individual's risk
of cancer and providing a tailored prevention strategy will be the cornerstones of a truly effective cancer prevention effort. NCI is
actively working toward that goal.

Understanding the Risk of Developing Cancer: The NCI Cohort Consortium

The study of genetic and environmental risk factors for cancer has advanced considerably due to our investment in population studies.
Researchers are using new genomic technologies, pooling resources, and sharing findings from large-scale studies, which are identifying
gene variants that affect cancer risk, diagnosis, and prognosis. Underpinning the success of these studies is a long-term investment in
the NCI Cohort Consortium. Comprised of 32 separate study
groups including 4 million people, this cooperative, international endeavor collects biological specimens and associated risk factor data
from a diverse group of populations. It provides a coordinated, interdisciplinary approach to tackling important scientific questions,
while affording opportunities to quicken the pace of research and work across a collaborative network of investigators.

To assess the cancer prevention properties of promising drugs and other agents, NCI is funding six chemoprevention research consortia.
These groups will design and conduct Phase I and Phase II clinical trials, which determine safety and efficacy. The ultimate goal is to
identify agents and strategies that can be tested in larger Phase III trials to determine whether a drug meets criteria for FDA approval.
Consortia researchers will study the effects of these agents on molecular targets of cancer prevention, as well as on other biological
events associated with cancer development, such as cell proliferation, cell death, the expression of growth factors, and the development
of genes that cause cancer. Researchers will also correlate effects of the agents with clinical outcomes of trials, including survival and
disease progression. The first 18 early-phase chemoprevention trials are now accruing patients and the consortia are developing 17 more
trials.